Recent advances in the use of genetically engineered vaccines to prevent outbreaks of infectious diseases have prompted a re-evaluation of vaccination strategies against a number of pathogens. We have been developing a new method of immunization that is based on a flexible antigen delivery platform technology that provides highly effective immune responses to a wide range of antigens. Following selection of a potential target antigen, the antigenic segment is genetically fused with a hydrophobic protein domain that has been engineered to associate with liposomal membranes. The fusion protein is water soluble under the appropriate conditions, allowing for the isolation and manipulation of the recombinant protein using commercially viable preparative procedures. We have previously shown that this liposome-based system of vaccination is highly effective in stimulating active immune protective responses in rodents against viral and bacterial pathogens. We intend to extend these results to fungal pathogens in this proposal. For this purpose, we have selected Aspergillus fumigatus, a common fungus that causes a devastating disease, invasive aspergillosis, primarily in people whose immune system has been compromised. Patients hospitalized with this condition have lengthy hospital stays and high mortality rates. Illnesses caused by Aspergillus engender a significant economic burden in the US, every other developed country, and many developing nations every year. Moreover, this burden is growing and, as documented in many epidemiologic studies, would be expected considering the increased numbers and survival of immunocompromised persons. Thus, a safe and effective vaccine against A. fumigatus would save health care dollars (and have significant dollar value) and, most importantly, save lives. While vaccinating an immunocompromised host would appear to be a formidable task, Aspergillus virulence factors/immunogens have now been identified that could serve as valid targets for vaccine development. With the determination of the genomic sequences of these target antigens and a much better understanding of the cytokine network, we believe that our immunization technology could successfully be used to engineer a vaccine that would generate protective host immune responses. Some of the more likely clinical scenarios in which we envision that such a vaccine would be effectively utilized are in the immunocompromised patient or the immunization of a stem cell donor. We have been developing a new method of immunization that is based on a flexible antigen delivery platform technology designed to elicit highly effective immune responses to a wide range of pathogens. This application proposes to utilize this vaccine technology to engineer a vaccine against fungal pathogens. For this purpose, we have selected Aspergillus fumigatus, a common fungus that causes a devastating disease, invasive aspergillosis, primarily in people whose immune system has been compromised. Patients hospitalized with this condition have lengthy hospital stays and high mortality rates. Illnesses caused by Aspergillus engender a significant economic burden in the US, every other developed country, and many developing nations every year. Moreover, this burden is growing and, as documented in many epidemiologic studies, would be expected considering the increased numbers and survival of immunocompromised persons. Thus, a safe and effective vaccine against A. fumigatus would save health care dollars (and have significant dollar value) and, most importantly, save lives. [unreadable] [unreadable] [unreadable]